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ENVIRONMENTALLY RESPONSIVE PEPTIDES AS ANTICANCER DRUG
CARRIERS
AND
REVERSIBLE LIPOSOME STABILIZATION WITH ENVIRONMENTALLY
RESPONSIVE POLYPEPTIDES
by
Suhaas Rayudu Aluri
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(PHARMACEUTICAL SCIENCES)
August 2010
Copyright 2010 Suhaas Rayudu Aluri
Object Description
| Title | Environmentally responsive peptides as anticancer drug carriers; and, Reversible liposome stabilization with environmentally responsive polypeptides |
| Author | Aluri, Suhaas Rayudu |
| Author email | saluri@usc.edu; suhaas.rayudu@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pharmaceutical Sciences |
| School | School of Pharmacy |
| Date defended/completed | 2010-05-14 |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-08-06 |
| Advisor (committee chair) | Mackay, John Andrew |
| Advisor (committee member) |
Okamoto, Curtis Camarero, Julio A. |
| Abstract | Chapter 1: The tumor microenvironment provides multiple cues that may be exploited to improve the efficacy of established chemotherapeutics; furthermore,polypeptides are uniquely situated to capitalize on these signals. Peptides provide: 1) a rich repertoire of biologically specific interactions to draw upon; 2)environmentally-responsive phase behaviors, which may be tuned to respond to signatures of disease; 3) opportunities to direct self-assembly; 4) control over routes of biodegradation; 5) the option to seamlessly combine functionalities into a single polymer via a one-step biosynthesis. As development of cancer-targeted nanocarriers expands, peptides provide a unique source of functional units that may target disease. This dissertation explores potential microenvironmental physiology indicative of tumors and peptides that have demonstrated an ability to target and deliver to these signals.; Chapter 2: While some amphipathic peptides interact directly with membranes, many peptides have potentially useful environmentally-responsive behavior only in aqueous solution. We developed a simple approach to modify water-soluble polypeptides via an amino terminal lysine using two palmitoyl lipids. As a model polypeptide, we used our approach to graft short elastin like polypeptide (ELPs)sequences to the surface of liposomes. High molecular weight ELPs undergo an environmentally responsive phase transition, whereby they phase separate from water above a critical transition temperature. The phase transition of free ELPs does not induce leakage of membranes; however, the incorporation of two proximal lipid groups to the free amines on a terminal lysine residue were able to reversibly stabilize a lipid membrane. After developing this new strategy for grafting peptides to the surface of a liposome, we observed that these liposomes were stable near body temperature and can be triggered to release 100% of their encapsulated contents within a few minutes. This new formulation has potential as a new bioresponsive drug carrier, which may promote controlled release to cancer. |
| Keyword | drug delivery; liposomes; peptides; cancer; hyperthermia |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3323 |
| Rights | Aluri, Suhaas Rayudu |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Aluri-3861 |
| Archival file | uscthesesreloadpub_Volume29/etd-Aluri-3861.pdf |
Description
| Title | Page 1 |
| Full text | ENVIRONMENTALLY RESPONSIVE PEPTIDES AS ANTICANCER DRUG CARRIERS AND REVERSIBLE LIPOSOME STABILIZATION WITH ENVIRONMENTALLY RESPONSIVE POLYPEPTIDES by Suhaas Rayudu Aluri A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (PHARMACEUTICAL SCIENCES) August 2010 Copyright 2010 Suhaas Rayudu Aluri |
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